The glutathione content of blood and tissues following alloxan and dehydroascorbic acid injections.

The mechanism of the production of diabetes in animals given injections of alloxan has been the subject of much study in recent years. Since the original publication of Dunn, Sheehan & McLetchie (1943) it has been established that the diabetes is pancreatic in origin but the chemical mechanisms involved have remained in doubt. Leech & Bailey (1945), using the arsenophosphotungstic acid method, were among the first to observe a precipitous but temporary fall in the concentration of glutathione in the blood of rabbits after the intravenous injection of diabetogenic amounts of alloxan. Since then other workers (Bruckmann & Wertheimer, 1947; Binet, Wellers & Marquis,1949; Collin-Williams, Renold & Marble, 1950) have reported similar falls in glutathione in the blood of rats and guinea pigs after alloxan injection, though the guinea pigs do not develop diabetes (West & Highet, 1948). On the basis of these observations upon blood glutathione concentration and other circumstantial evidence, Lazarow (1949) suggested that alloxan forms an addition compound with sulphydryl groups in the ,B cells of the islets of Langerhans, so causing death of these cells. Certain structural similarities between dehydroascorbic acid (DHA) and alloxan suggested that the former compound might also be diabetogenic. Patterson (1949, 1950) was the first to report the production of diabetes in rats given large amounts of DHA by intravenous injection. Lazarow (1954) in particular has suggested that the mechanism of the production of diabetes by DHA may be similar to that by alloxan and cites evidence in support of this view. Measurements have therefore been made, and are recorded in this paper, of the concentration of glutathione in the blood and tissues of rats and in the blood of rabbits following the intravenous injection of alloxan and DHA. In the former animals both substances are diabetogenic and produce histological changes in the islet cells of the pancreas (MacDonald & Bhattacharya, 1956). Since, in these experiments, the specific glyoxalase method of Dohan & Woodward (1939), as modified by Bhattacharya, Robson & Stewart (1955) for the determination of glutathione (GSH), oxidized glutathione (GSSG) and total glutathione (GSH+ GSSG), was employed, opportunity was taken to repeat the experiments of Leech & Bailey with alloxan and to extend the observations to include tissue analyses.